Treatment of Glaucoma Patients with Flammer Syndrome

Flammer syndrome (FS) describes a phenotype characterized by the presence of primary vascular dysregulation along with a number of symptoms and signs. Although most people with FS are healthy, FS favors the occurrence of certain diseases, such as normal tension glaucoma. This is because disturbed autoregulation makes the eye more sensitive to intraocular pressure (IOP) spikes or blood pressure drops. Treatment of FS is generally appropriate when patients either suffer greatly from their symptoms or if we can assume that it has contributed to a disease. In glaucoma, this may be the case if the glaucoma damage progresses despite well-controlled IOP. Both the still sparse scientific studies and our long clinical experience suggest that FS-targeted therapy not only relieves the symptoms of FS but also slows the progression of glaucoma damage in selected cases. This description is intended not only to help affected patients but to also motivate clinicians and researchers to conduct therapy studies to confirm or refute our observations.

Systemic Vascular Dysregulation May Be Associated With Lower Peripapillary Vessel Density in Non-glaucomatous Healthy Eyes: A Prospective Cross-Sectional Study

Objective: To determine whether systemic vascular dysregulation (SVD) evaluated by nailfold capillaroscope and Flammer Syndrome Questionnaire (FSQ) affects retinal peripapillary microcirculation in non-glaucomatous healthy eyes at steady status.Methods: 120 healthy eyes from 63 non-glaucomatous subjects underwent Optical coherence tomography angiography (OCTA) after a rest of 30 minutes. Average retinal peripapillary capillary (RPC) vessel density (VD) and sectoral VD were automatically calculated, and peripapillary retinal nerve fiber layer thickness (RNFLT) was measured. Vasospastic diathesis was assessed using Flammer Syndrome Questionnaire (FSQ). Cold provocation test (CPT) was performed using nail-fold capillaroscope after OCTA. Positive CPT and a score of FSQ higher than 20% were necessary to determine a subject with SVD. Systemic and ocular parameters were compared between subjects with and without SVD.Results: In this study, heart rate (p = 0.042), ocular perfusion pressure (p = 0.014) and average RPC vessel density (p = 0.046) was significantly different between subjects with and without SVD determined by the combination of CPT and FSQ. Generalized estimation equation (GEE) showed lower VD was significantly associated with longer axial length (β = −0.352, p = 0.001), thinner peripapillary retinal nerve fiber layer thickness (RNFLT) (β = 0.296, p < 0.001), SVD determined by CPT and FSQ (β = 0.617, p = 0.003) and high blood pressure (β = −0.879, p < 0.001). In the superotemporal sector, multivariate model showed only SVD was associated with RPC vessel density (β = −0.811, p < 0.001).Conclusion: In subjects with SVD and non-glaucomatous healthy eyes, lower RPC vessel density in the superotemporal sector was observed. SVD determined by CPT and FSQ was significantly associated with attenuated retinal peripapillary microcirculation. Studies on ocular diseases relevant to vasospasms should consider the effects of SVD on the retinal peripapillary capillaries.

AB0961 MYOFASCIAL TRIGGER POINTS ARE THE UNDEREVALUATED HYPOXIC NISCHES ALTERING POSTURE AND PHENOTYPE

Objectives:Myofascial trigger point (MTrP) is a pillar pathophysiological unit in development of myofascial pain [1] and postural imbalance [2]. Dry needling (DN) of MTrP under ultrasound (US) guidance is prioritized method for treatment myofascial pain. Hypoxia-related signaling pathways play important role in development of rheumatic diseases and cancer [3,4].Hypothesis:MTrP are spastic hypovascularized hypoxic low energy areas that can produce organismic signaling, associated with niches in Flammer syndrome [3,4].Objectives:The aimwas to evaluate structure of MTrP in regard to stiffness and “ischemic pattern” before and after DN.Methods:We included 40 patients (26 females, aged 18–68 y.o.) with low back pain. Healthy 20 individuals (aged 18–52 y.o.) were controls. All patients underwent general exam, MRI, precise physical tests, extensive functional multiparameter neuromuscular US including M-mode, elastography (SWE), B-Flow (LOGIC E9 GE) of multifidus muscles. Then patients received DN of detected MTrP under US guidance.Results:We successfully detected MTrP as hypoechoic, stiff and hypovascular small areas with different patterns of decreasing motility, contractility (muscle contracted/rested thickness) in all patient and did precise DN. After DN muscle structure improved, motility, contractility restored, VAS scores changed from 7.4 to 2.3 (p <0.05). SWE was 11±6 kPa in MTrP (27 kPa in active, 5-8 kPa in latent MTrP) vs 3.8±0.3 kPa in controls and decreased to 4±0.4 kPa after treatment. Hypovascularity (“ischemic pattern”) size decreased from 3-4 mm to 0-1.5 mm, correlated with muscle function. Preliminary we found MTrP with more expressed hypovascular pattern, higher sensitivity and retaining levels of in individuals lower BMI and patient with Flammer phenotype [3,4] (13-15/15 positive responses to questionnaire).Conclusion:MTrP are stiff and most likely hypoxic areas, parameters improved after precise DN. US hunting for “ischemic pattern” markers can be important for patient stratification and targeted treatment and prevention. Metabolic profiling including HIF signaling, proteomic data collecting needed for further investigation for effective patients stratification. For the follow-up studies a correlation of the Flammer syndrome phenotype with individualised profiles of patients and diagnosed ischaemic patterns is recommended.References:[1]Bubnov RV: Evidence-based pain management: is the concept of integrative medicine applicable? EPMA J 2012; 3(1):13.[2]Bubnov R, Kalika L. EFFECTIVE RESTORING MOTION AND EFFECTIVE TREATMENT OF MYOFASCIAL AND NEUROPATHIC LOW BACK PAIN BY TARGETED DRY NEEDLING USING ULTRASOUND GUIDANCE. Annals of the Rheumatic Diseases 2019;78:1921-1922.http://dx.doi.org/10.1136/annrheumdis-2019-eular.5533[3]Flammer Syndrome: From Phenotype to Associated Pathologies, Prediction, Prevention and Personalisation. Ed. by Olga Golubnitschaja. Springer International Publishing, 2019: 340.4.Bubnov R, Polivka J, Zubor P, Konieczka K, Golubnitschaja O. “Pre-metastatic niches” in breast cancer: are they created by or prior to the tumour onset? “Flammer syndrome” relevance to address the question. EPMA J. 2017;8(2):141–57.Disclosure of Interests:None declared

Flammer Syndrome & Glaucoma

The need of blood flow to different organs varies rapidly over time which is why there is a need for sophisticated local regulation of blood flow. The term “dysregulation” just simply means that blood flow is not properly adapted to this need. Dysregulative mechanisms can therefore lead to an over- or under-perfusion. A constant over- or under-perfusion does not normally induce long-term damage. A repeated under-perfusion, such as a repeated mild reperfusion injury, however, leads to damage. Systemic dysregulation can be primary or secondary of nature. A secondary dysregulation (SVD) is due to other diseases such as autoimmune diseases. The term Flammer Syndrome (FS) named after the famous physician J. Flammer refers to a clinical entity comprising a complex of clinical features caused mainly by dysregulation of the blood supply which has previously been called primary vascular dysregulation. People with FS tend to have cold extremities, prolonged sleep-onset time, altered drug sensitivity, low blood pressure and higher smell score, and increased retinal venous pressures as measured by means of ophthalmodynamometry. In the eye, the spatial irregularity of the retinal arteries is increased, and optic nerve head blood flow is correlated with finger blood flow indirectly indicating that the local regulation is disturbed. Blood flow is, on average, reduced in glaucoma patients, particularly in patients with normal-tension glaucoma suffering from FS, and in patients with high-tension glaucoma, which progress despite a normalized intraocular pressure (IOP). A constant reduction of blood flow (as we see in SVD) can lead to atrophy but does not contribute to glaucomatous atrophy. An increased variation of microcirculation as commonly seen in glaucoma patients with FS, however, is clearly linked to occurrence and progression of glaucomatous optic neuropathy (GON). Oxygen supply to the eye fluctuates, either if IOP fluctuates on a high level or blood pressure on a low level or if autoregulation is disturbed. Autoregulation is disturbed in patients with primary vascular dysregulation (PVD). Unstable oxygen supply to the optic nerve head leads to oxidative stress, which in turn, leads to the production of peroxynitrite (ONOO-) which finally kills the cells. In this review, we are talking about pathogenesis of the FS and some suggested therapeutic options for it.